An interesting small study shows hepcidin levels in RLS patients were higher than in control group.
Hepcidin decreases the level of iron by reducing dietary absorption and inhibiting iron release from cellular storage. Hepcidin production increases when iron levels rise above the normal range of 65 to 175 mcg/dL in males and 50 to 170 mcg/dL in females.
So it could explain why RLS patients struggle to raise iron levels in the brain.
The study does say more studies are needed to confirm the findings.
That's interesting and not surprising since as I'm sure you know taking iron tablets causes hepcidin to be released which prevents one from absorbing more iron for 24 hours. Which is why it is stupid for doctors to say to take iron 2 to 3 times a day.
I might be reading it wrong, but it seems that hepcidin is virtually identical between the two groups if you look at the data box.
There’s this article which states that hepcidin is the same when compared to controls:
Of course that could explain why Vitamin D helps RLS so much.
Sleep Medicine: A peer-reviewed journal article published in Sleep Medicine in 2015 found that vitamin D supplementation significantly improved RLS symptoms in patients with vitamin D deficiency.
PLOS One: A peer-reviewed journal article published in PLOS One in 2016 found that vitamin D supplementation was effective in reducing RLS symptoms in patients with chronic kidney disease.
Journal of Clinical Sleep Medicine: A peer-reviewed journal article published in the Journal of Clinical Sleep Medicine in 2017 found that vitamin D supplementation improved RLS symptoms and sleep quality in patients with moderate to severe RLS.
Neurology: A peer-reviewed journal article published in Neurology in 2018 found that vitamin D supplementation was associated with a reduction in RLS symptoms in patients with Parkinson's disease.
OH man, I hate it when people call me out on this stuff... just kidding, we should always do this. I knew I should have put them there at the start. I hope I can find all the links.
4) Sorry I can't find this one in my notes.... but there are a lot to choose from
"Effect of vitamin D supplementation on the severity of restless legs syndrome in patients with Parkinson's disease: a randomized, double-blind, placebo-controlled trial" (2015) by Wali et al., published in the journal Sleep and Breathing (link: ncbi.nlm.nih.gov/pmc/articl...
"Vitamin D supplementation improves restless legs syndrome in patients with Parkinson's disease: a pilot study" (2017) by Yildirim et al., published in the journal Parkinson's Disease (link: ncbi.nlm.nih.gov/pmc/articl...
"Vitamin D supplementation improves restless legs syndrome symptoms in patients with Parkinson's disease: a case-control study" (2020) by Yilmaz et al., published in the journal Neurological Sciences (link: ncbi.nlm.nih.gov/pmc/articl...
"Vitamin D and restless legs syndrome in Parkinson's disease: a systematic review and meta-analysis" (2021) by Zhang et al., published in the journal Parkinsonism & Related Disorders (link: ncbi.nlm.nih.gov/pmc/articl...
"Vitamin D and restless legs syndrome in Parkinson's disease: a prospective observational study" (2022) by Yilmaz et al., published in the journal Frontiers in Neurology (link: ncbi.nlm.nih.gov/pmc/articl...
I spoke with a top Parkinson's professor at Bart's on Friday and he astonished me by saying his team no longer prescribe dopamine agonists for Parkinson's. Mainly because of high rates of Augmentation and ICD.There is hope.
Little by little, the knowledge is getting out there.
Oh my, I don't have time for this rabbit hole. It took me a bit, but I see it. Good catch. I am still trying to figure out Table 3 and statistics was never my favorite. If anyone can explain that, I would be open.
Clearly there is a connection between hepcidin and iron. My frustration is, I don't see an option on my blood test to test for Hepcidin. I know when I started years ago, my Vitamin D was 24. After years of massive does 10000IU plus daily and more. Not to mention all the time I spend in the sun, I got my Vitamin D to 64. It would be very interesting to know how much that impacted hepcidin levels.
The more we learn, the more we learn about stuff we don't have answers too.
64 is great! Like iron, Vitamin D is very tightly controlled. Your skin will only absorb so much and I believe same is true for the gut. Hepcidin has a circadian rhythm, as does iron, but they’re inverse, kind of. Hepcidin rises through-out the day and scavanges iron which plummets 60% or more by midnight, leading to our RLS. Hepcidin starts to be low at early evening hence the reason some smart doctors recommend we take iron at night to maximize absorption. Do you think the iron provides you with immediate relief each night from RLS, or do you think it’s your ferritin level that provides you with relief.
"Do you think the iron provides you with immediate relief each night from RLS, or do you think it’s your ferritin level that provides you with relief."
For me I think it is both. When I first started a long time ago. My ferritin was a 7. I took liquid ferrous sulfate everyday for a year. Sadly, I took it in the morning with coffee and a vitamin c. No one told me the right way. I got my ferritin to over 200. It did nothing for my RLS. The nurse suggested I stop taking iron. It took 18 months for my Ferritin to fall to 30. (I have an excel spreadsheet).
Once I noticed the fall, I went to the Doctor and asked for an infusion. They agreed. I got 5 infusions of 200mg Iron Sucrose. (not the best choice, but I was winging it and desperate) It was the best damn thing that ever happened for my RLS, it was a decade late.
I now notice a reduction in symptoms if I take ferrous bisglysinate about 2 -3 hours before bed. Probably even closer to three hours. I think it takes time for the body to process the iron. I think timing is VERY important, if the goal is to minimize symptoms at bed time.
But you see, you got your ferritin to 200 via oral iron and by your own admission it did nothing for your RLS. Then an infusion two years later got your iron back up there, but you feel it made a world of difference? 200 ferritin is 200 ferritin, no matter how we get it to that point, right? Is it possible that some other factor you started (or stopped) around the time of the infusion contributed to your well-being? I checked and it sounds as though your ferritin is in the 70s right now, yet you’re mostly RLS free??? I’m happy for you WideBody.
I think I know what happened. You were taking ferrous sulfate in the morning so it had no immediate effect at night AND you were on the dreaded DAs at the time. You stopped the oral iron and back down went your ferritin to 30. A few weeks (months?) before the iron infusion(s) you quit the DAs cold Turkey. Having low iron stores at this point you were given an iron infusion and bam away went the augmentation…or greatly reduced. I have read in multiple articles that iron deficiency will worsen the symptoms of augmentation. I read one article where they gave iron infusions to people augmenting on the DAs and it took away the augmentation and they were able to continue on with the DAs. I believe that had you maintained your ferritin all along then after you stopped the DAs (and given Gabapentin) you would have been in the same “good-Ish” place a few months later as you were after the infusion. Does that make sense?
Clinical Anesthesia (SAE): This textbook states that "vitamin D blocks hepcidin production, a hormone that inhibits iron absorption." (Source: books.google.com/books?id=M...
Frontiers in Physiology: This peer-reviewed journal article states that "vitamin D deficiency has been shown to increase hepcidin levels, which can lead to iron deficiency anemia." (Source: frontiersin.org/articles/10...
PMC - NCBI: This peer-reviewed journal article states that "vitamin D deficiency is a common cause of anemia, and vitamin D supplementation has been shown to improve iron absorption and reduce hepcidin levels." (Source: ncbi.nlm.nih.gov/pmc/articl...
In addition to these sources, a number of clinical trials have also shown that vitamin D supplementation can reduce hepcidin levels. For example, a 2018 study published in the journal Nutrients found that vitamin D supplementation for 12 weeks significantly reduced hepcidin levels in people with chronic kidney disease.
It has been harder for me to raise my Vitamin D than it has been to raise my ferritin.
There is more here than 99.99% of doctors know about vit D, hepcidin, iron and RLS. Including me and i have an interest in writing a course for doctors on RLS!
I'm so grateful that you are writing a course for doctors. I hope you can get through the barriers.Kakally has come across lots of resistance to medical training here in the UK.
I also started a campaign to have RLS taught properly a few year's ago and the RCGPs refused. They have now 'ghosted' RLS UK and won't respond to emails.
I would be happy to help with your course as far as iron goes. I have done a bit of research. I can also have experience with the hell of augmentation, and brain fog of gabapentin, pregabalin and also the Joy of Dipyridamole.
Interesting. Although I am not female, I certainly can relate to 3-5 hour endurance events. I still do them regularly at 63. I read a study years ago, "Perceived exertion was less if supplementing with iron prior to the events." I may have tried it. However, it is more important for me to supplement about 2 hours prior to bed now.
I think that’s why you’re doing so well. Exercise, especially anaerobic, is supposed to up-regulate our receptors, and as long as done in the morning shouldn’t affect RLS that night. I think that has helped Bax as well. It’s the DAs that screw people up. Had you done the iron at night thing from the gitgo, that would likely have been enough. That’s why I’m on here banging the drum. It’s NOT enough to tell people to raise their ferritin. It’s a very precise, scientific, cosmic gift from above. Iron, the right kind, in the right amount, taken at the right time on an empty stomach will relieve RLS in one hour. I wish the regulars on here would join in my parade.
Kelka is one of the more interesting cases I’ve seen on here during my 10 year tenure. She would have to hurl herself off the stationary bicycle when she got to that anaerobic moment because the RLS was so intense. No pain no gain. Upregulating our receptors can be a painful process, but ultimately is probably the best treatment. I wish I knew then what I know now. I believe her RLS was caused by antidepressants.
If inflammation causes high hepcidin and hepicidin supresses ferritin then why does inflammation cause an unrepresentative high ferritin measurement? Is the high ferritin measurement a real measurement of the ferritin concentration or does something to do with inflammation corrupt the measurement process? (Perhaps the ferritin analysis gives a false result because of the high hepciden concentration. Just to be confusing)
I've never investigated that because I've never had confidence in the hypothesis that RLS is caused by levels of iron or ferritin due to the fact that some people get positive results from infusions and some don't. My hypothesis is that RLS and the levels of iron or ferririn are all caused by inflammation or the diets, infections, toxins etc. that cause inflammation. I have proven that in myself because I have eliminated my RLS without drugs but by merely avoiding all inflammatory foods. If you search the internet you will find lists of inflammatory foods. there are minor variations in that some list red meat as inflammatory which I've never found in myself.
Thanks Graham, In case people are not familiar with it researchgate.net is very useful for finding articles. Especially if you start with a title like the one above, it finds it, usually you can download it, or contact the author and ask them to email it to you and then it finds all related articles. 3 hours later you can come up for air...
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Ever wonder why those IV iron infusions didn't do a thing for your RLS? Note last paragraph of abstract..IV infusions BLOCK iron absorption!
The link between Iron and RLS
Iron infusion rls
Would oral iron be useful given my Iron levels (in description)?
